GLYCOLIPID ENRICHED MEMBRANE DOMAINS IN HIV BIOLOGY

描述（改编自申请人摘要）：本研究的中心假设 建议是宿主细胞膜的专门区域， 脂质图的糖脂富集膜（GEM）域在脂质代谢中起着重要的作用。 在HIV-1的进入和萌芽阶段的生物学作用， 病毒复制周期目标是确定脂筏在HIV中的作用 复制和分析一些重要的生物后果。的 具体目标是：1）将早期对HIV GEM域出芽的研究扩展到 原代细胞和CCR 5特异性病毒; 2）为了确定GEM结构域是否 艾滋病毒进入的首选地点。这些研究将检查CD 4的分类， 和趋化因子受体对GEM结构域的作用， 分子是病毒进入所必需的; 3）为了确定GPI是否锚定和 棕榈酰化是HIV掺入蛋白质的信号。GPI锚 和棕榈酰化已经成为膜分类的两个关键信号 域到GEM域。这些研究将确定这些信号是否 特异性靶向病毒编码和宿主细胞膜蛋白， 4）确定GEM结构域分散的影响 艾滋病毒的萌芽和进入。这些研究将通过胆固醇破坏GEM结构域 消耗和抑制鞘脂合成，并分析对 HIV进入和出芽; 5）确定GEM结构域的分散效果 内部传单上艾滋病毒的萌芽和进入。这些研究将使用多不饱和 脂肪酸修饰的GEM结构域的内部小叶，以确定 它们在艾滋病毒萌芽和进入中的作用。这些研究的结果应提供 对HIV宿主膜相互作用的有价值的新见解，并可能提供 新的抗病毒疗法的基础。

Description (Adapted from Applicant's abstract): The central hypothesis of this proposal is that specialized regions of the host cell membrane known as glycolipid-enriched membrane (GEM) domains of lipid graphs play an important role in the biology of HIV-1 during both the entry and budding phases of the virus replication cycle. The goals are to define the role of lipid rafts in HIV replication and to analyze some of the important biological consequences. The specific aims are: 1) To extend early studies on HIV GEM domain budding to primary cells and CCR5-specific virus; 2) To determine whether GEM domains are preferred sites for HIV entry. These studies will examine the sorting of CD4 and chemokine receptors to GEM domains and whether such sorting of either molecule is necessary for virus entry; 3) To determine whether GPI anchors and palmitoylation are signals for incorporation of proteins by HIV. GPI anchors and palmitoylation have emerged as two key signals for sorting of membrane domains to GEM domains. These studies will determine whether these signals specifically target virus-encoded and host cell membrane proteins for incorporation by HIV; 4) To determine the effects of dispersion of GEM domains on HIV budding and entry. These studies will disrupt GEM domains by cholesterol depletion and inhibition of sphingolipid synthesis and analyze the effects on HIV entry and budding; 5) To determine the effect of dispersion of GEM domain inner leaflets on HIV budding and entry. These studies will use polyunsaturated fatty acids to modify the structure of GEM domain inner leaflets to determine their role in HIV budding and entry. Results of these studies should provide valuable new insights into HIV host membrane interactions and may provide the basis for novel anti-viral therapeutics.